TcR‐induced regulated secretion leads to surface expression of CTLA‐4 in CD4<sup>+</sup>CD25<sup>+</sup> T cells

Catálfamo, Marta; Tai, Xuguang; Karpova, Tatiana S.; McNally, James G.; Henkart, Pierre A.

doi:10.1111/j.1365-2567.2008.02822.x

Cited by 21 publications

(19 citation statements)

References 31 publications

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“…We also observed low-level expression of markers previously associated with Tregs such as CTLA4 (21,31), in which our data show only a small number of cells constitutively expressed CTLA4 at the cell surface. This could be due to using cells directly ex vivo in our study, with no stimulation performed and restricting our phenotypic analysis to surface-bound expression, which would not detect preformed CTLA4 present in intracellular vesicles or those trafficked to the cell surface after T cell activation, which has been shown in human Tregs previously (32,33).…”

Section: Discussionmentioning

confidence: 92%

Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry

Mason

Lowe

Melchiotti

et al. 2015

The Journal of Immunology

126

113

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Regulatory T cells (Tregs) are an essential component of the cellular immune response, occupying a key role in maintaining immunological tolerance and present an attractive therapeutic target in a range of immunopathologies. Comprehensive analysis of the human Treg compartment has been restricted due to technical limitations. The advent of mass cytometry enables simultaneous assessment of vastly increased phenotypic parameters at single-cell resolution. In this study, we used mass cytometry to examine the complexity of human Tregs using an extensive panel of surface markers associated with Treg function and phenotype. We applied unsupervised clustering analysis, revealing 22 distinct subpopulations of Tregs, representing previously identified and novel subpopulations. Our data represent the most in-depth phenotypic description of the human Treg compartment at single-cell resolution and show a hitherto unrecognized degree of phenotypic complexity among cells of the regulatory lineage.

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Section: Discussionmentioning

confidence: 92%

Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry

Mason

Lowe

Melchiotti

et al. 2015

The Journal of Immunology

126

113

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“…The detection of co-localization of CTLA-4 with lysosomal compartments using antibody markers has generally been variable (15, 16). This likely reflects the fact that CTLA-4 is rather rapidly degraded, and consequently co-localization is difficult to observe.…”

Section: Discussionmentioning

confidence: 99%

“…T cell activation is then thought to deliver CTLA-4 to the cell surface from an intracellular compartment (10, 13–16) in a manner that may be proportional to the intensity of T cell receptor signaling (17). However, the fate of CTLA-4 subsequent to T cell receptor-driven up-regulation is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Constitutive Clathrin-mediated Endocytosis of CTLA-4 Persists during T Cell Activation

Qureshi

Kaur

Hou

et al. 2012

Journal of Biological Chemistry

145

121

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“…59 Tregs are characterized by the expression of the FOXP3 transcription factor with greater expression of the negative co-stimulatory molecule cytotoxic T lymphocyte-associated antigen 4. 60 The number of Tregs in the peripheral blood of MDS patients has been shown to positively correlate with risk for disease progression. Further investigation is needed to determine whether the number and/or function of Tregs is lower in IST-responsive patients compared with healthy controls with age adjustment.…”

Section: Discussionmentioning

confidence: 99%

Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome

Boulware

et al. 2009

Leukemia

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Response to immunosuppressive therapy (IST) in younger patients with myelodysplastic syndrome (MDS) has been linked to a T-cell-dominant autoimmune process that impairs hematopoiesis. Analysis of the age-adjusted CD4:CD8 ratio in 76 MDS patients compared with 54 healthy controls showed that inadequate CD4+, rather than expansion of CD8+ T cells, was associated with a lower ratio in a group that included both lower and higher risk MDS patients defined by the International Prognostic Scoring System. In younger MDS patients, naive and memory phenotypes defined by CD45RA and CD62L display showed depletion of naive CD4+ and CD8+ T cells, suggesting a possible relationship to IST responsiveness. To determine the correlation between T-cell subset distribution, T-cell turnover and autoimmunity, a cohort of 20 patients were studied before and after IST. The CD4:CD8 ratio correlated inversely with the proliferative T-cell index before treatment in IST-responsive patients, suggesting that proliferation may be linked to accelerated CD4+ T-cell turnover and hematopoietic failure. Our data show seminal findings that both CD4+ and CD8+ T-cell subsets are dysregulated in MDS. Association between these T-cell defects and response to IST suggests that aberrant T-cell homeostasis and chronic activation are critical determinants influencing autoimmune hematopoietic suppression in younger patients.

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TcR‐induced regulated secretion leads to surface expression of CTLA‐4 in CD4⁺CD25⁺ T cells

Cited by 21 publications

References 31 publications

Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry

Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry

Constitutive Clathrin-mediated Endocytosis of CTLA-4 Persists during T Cell Activation

Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome

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TcR‐induced regulated secretion leads to surface expression of CTLA‐4 in CD4+CD25+ T cells

Cited by 21 publications

References 31 publications

Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry

Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass Cytometry

Constitutive Clathrin-mediated Endocytosis of CTLA-4 Persists during T Cell Activation

Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome

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TcR‐induced regulated secretion leads to surface expression of CTLA‐4 in CD4⁺CD25⁺ T cells